Na+ channel protein type 10 subunit alpha; Na+ channel protein type X subunit alpha; voltage-gated Na+ channel subunit alpha Nav1.8; peripheral nerve Na+ channel 3; hPN3 (SCN10A, PN3)
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Function
- mediates voltage-dependent Na+ permeability of excitable membranes
- assumes opened or closed conformation in response to voltage difference across the membrane
- forms a Na+-selective channel through which Na+ may pass in accordance with their electrochemical gradient
- tetrodotoxin-resistant Na+ channel isoform
- electrophysiological properties vary depending on the type of the associated beta subunits (in vitro)
- ubiquitinated by NEDD4L; which promotes its endocytosis
- voltage-resistant Na+ channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B & SCN3B
- found in a number of complexes with PRX, TCTEL1 & PDZD2
- interacts with proteins such as FSTL1, PRX, TCTEL1, PDZD2, S100A10 & many others (putative). interacts with NEDD4 & NEDD4L
Structure
- contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) & one positively charged segment (S4)
- segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every third position
- belongs to the Na+ channel family
- contains 1 IQ domain
Compartment
- membrane
- translocated to extracellular membrane through association with S100A10 (putative)
Expression
- expressed in the dorsal root ganglia & sciatic nerve
Pathology
- plays a role in neuropathic pain mechanisms (putative)
Pharmacology
- VX-548, an oral, highly selective inhibitor of NaV1.8 (SCN10A)[3]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9Y5Y9.html
- ↑ Rabert DK, Koch BD, Ilnicka M et al A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain. 1998 Nov;78(2):107-114. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9839820
- ↑ 3.0 3.1 Jones J, Correll DJ, Lechner SM et al Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37530822 Clinical Trial.